CS-PEG decorated PLGA nano-prototype for delivery of bioactive compounds: A novel approach for induction of apoptosis in HepG2 cell line

被引:65
作者
Abd-Rabou, Ahmed A. [1 ]
Ahmed, Hanaa H. [1 ]
机构
[1] Natl Res Ctr, Hormones Dept, Med Res Div, Giza 12622, Egypt
来源
ADVANCES IN MEDICAL SCIENCES | 2017年 / 62卷 / 02期
关键词
PLGA-CS-PEG nanoparticles; HepG2 cell line; Phytochemicals; Apoptosis; ACID INDUCES APOPTOSIS; PROSTATE-CANCER CELLS; IN-VITRO ANTIOXIDANT; PUNICA-GRANATUM L; FACTOR-KAPPA-B; ELLAGIC ACID; POMEGRANATE JUICE; ANTIPROLIFERATIVE ACTIVITY; BREAST-CANCER; SIGNALING PATHWAYS;
D O I
10.1016/j.advms.2017.01.003
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Purpose: Polymer-based nanoparticles are used as vectors for cancer drug delivery. The bioactive compounds (quercetin, ellagic acid and gallic acid) are well known to be not only antioxidants but also chemopreventive candidates against various types of cancers. To circumvent the low bioavailability and the short half-life time obstacles, we hypothesized a novel PLGA nano-platform functionalized with CS and PEG to encapsulate these phytochemicals. This encapsulation will protect the compounds from the phagocytic uptake and deliver PLGA-CS-PEG nano-prototype with high biodegradability and biosafety. Materials and methods: Three consequent types of PLGA-based nanocomposites were prepared and characterized. Furthermore, we investigated the newly synthesized nano-formulations against human hepatocellular carcinoma (HepG2) and colorectal cancer (HCT 116) cell lines using cell growth inhibition assays, followed by apoptosis and necrosis assays using flow cytometry to detect the underlying mechanism of HepG2 cell death. Results: Through Malvern Zeta Sizer, we recorded that the average diameters of the nano-prototypes ranged from 150 to 300 nm. The cytotoxic activity of quercetin, ellagic acid, and gallic acid-encapsulated PLGA, PLGA-CS, and PLGA-CS-PEG nano-prototypes it has been found that they reduce the IC50s of the HepG2 cells values by 2.2, 2.9, 2.8-folds, 1, 1.5, 2.7-folds, and 0.9, 0.7, 1.5-folds, respectively. Mechanistically, the nano-platforms of quercetin seem to be dependent on both apoptosis and necrosis, while those of ellagic acid and gallic acid are mainly dependent on apoptosis. Conclusions: CS-PEG-blended PLGA nano-delivery system of quercetin, ellagic acid and gallic acid can potentiate apoptosis-mediated cell death in HepG2 cell line. (C) 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:357 / 367
页数:11
相关论文
共 72 条
[1]  
Abd-Rabou A.A., 2016, INT J PHARM BIOL SCI, V4, pB584, DOI [10.22376/ijpbs.2016.7.4.b584-592, DOI 10.22376/IJPBS.2016.7.4.B584-592, DOI 10.22376/IJPBS.2016.7.4.B584-5923]
[2]   Potential impact of curcumin and taurine on human hepatoma cells using Huh-7 cell line [J].
Abd-Rabou, Ahmed A. ;
Zoheir, Khairy M. A. ;
Ahmed, Hanaa H. .
CLINICAL BIOCHEMISTRY, 2012, 45 (16-17) :1519-1521
[3]   Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells [J].
Adams, LS ;
Seeram, NP ;
Aggarwal, BB ;
Takada, Y ;
Sand, D ;
Heber, D .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2006, 54 (03) :980-985
[4]   Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model [J].
Adhami, Vaqar Mustafa ;
Siddiqui, Imtiaz Ahmad ;
Syed, Deeba N. ;
Lall, Rahul Kumar ;
Mukhtar, Hasan .
CARCINOGENESIS, 2012, 33 (03) :644-651
[5]   Cancer Chemoprevention by Pomegranate: Laboratory and Clinical Evidence [J].
Adhami, Vaqar Mustafa ;
Khan, Naghma ;
Mukhtar, Hasan .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2009, 61 (06) :811-815
[6]  
Ahmed Hanaa H, 2015, Asian Pac J Cancer Prev, V16, P7179
[7]   Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats [J].
Aiyer, Harini S. ;
Srinivasan, Cidambi ;
Gupta, Ramesh C. .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2008, 60 (02) :227-234
[8]   Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells [J].
Albrecht, M ;
Jiang, WG ;
Kumi-Diaka, J ;
Lansky, EP ;
Gommersall, LM ;
Patel, A ;
Mansel, RE ;
Neeman, I ;
Geldof, AA ;
Campbell, MJ .
JOURNAL OF MEDICINAL FOOD, 2004, 7 (03) :274-283
[9]   Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2) [J].
Alía, M ;
Mateos, R ;
Ramos, S ;
Lecumberri, E ;
Bravo, L ;
Goya, L .
EUROPEAN JOURNAL OF NUTRITION, 2006, 45 (01) :19-28
[10]   Synthesis of anionic poly(ethylene glycol) derivative for chitosan surface modification in blood-contacting applications [J].
Amiji, MM .
CARBOHYDRATE POLYMERS, 1997, 32 (3-4) :193-199